A review and meta-analysis of gene expression profiles in suicide

Ignazio S. Piras; Matthew J. Huentelman; Federica Pinna; Pasquale Paribello; Marco Solmi; Andrea Murru; Bernardo Carpiniello; Mirko Manchia; Clement C. Zai

doi:10.1016/j.euroneuro.2021.12.003

A review and meta-analysis of gene expression profiles in suicide

Ignazio S. Piras, Matthew J. Huentelman, Federica Pinna, Pasquale Paribello, Marco Solmi, Andrea Murru, Bernardo Carpiniello, Mirko Manchia, Clement C. Zai

Medicine

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

Abstract

Suicide claims over 800,000 deaths worldwide, making it a serious public health problem. The etiopathophysiology of suicide remains unclear and is highly complex, and postmortem gene expression studies can offer insights into the molecular biological mechanism underlying suicide. In the current study, we conducted a meta-analysis of postmortem brain gene expression in relation to suicide. We identified five gene expression datasets for postmortem orbitofrontal, prefrontal, or dorsolateral prefrontal cortical brain regions from the Gene Expression Omnibus repository. After quality control, the total sample size was 380 (141 suicide deaths and 239 deaths from other causes). We performed the analyses using two meta-analytic approaches. We further performed pathway and cell-set enrichment analyses. We found reduced expression of the KCNJ2 (Potassium Inwardly Rectifying Channel Subfamily J Member 2), A2M (Alpha-2-Macroglobulin), AGT (Angiotensinogen), PMP2 (Peripheral Myelin Protein 2), and VEZF1 (Vascular Endothelial Zinc Finger 1) genes (FDR p<0.05). Our findings support the involvement of astrocytes, stress response, immune system, and microglia in suicide. These findings will require further validation in additional large datasets.

Original language	English
Pages (from-to)	39-49
Number of pages	11
Journal	European Neuropsychopharmacology
Volume	56
DOIs	https://doi.org/10.1016/j.euroneuro.2021.12.003
Publication status	Published - Mar 2022

Bibliographical note

Funding Information:
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. MM, FP, and BC gratefully acknowledge the support from FIR 2019 and FIR 2020 of the Department of Medical Sciences and Public Health, University of Cagliari. AM thanks the support of the Spanish Ministry of Science and Innovation (PI19/00,672). CCZ was supported by the CAMH Foundation and by the Brain and Behavior Research Foundation. ISP was partially supported by a Sylvia B. Chase Early Career Research Award. The results published here are in part based on data obtained from the AD Knowledge Portal (https://adknowledgeportal.org). Study data were provided by the Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago. Data collection was supported through funding by NIA grants P30AG10161 (ROS) and RF1AG57473 (single nucleus RNAseq).

Funding Information:
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. MM, FP, and BC gratefully acknowledge the support from FIR 2019 and FIR 2020 of the Department of Medical Sciences and Public Health, University of Cagliari. AM thanks the support of the Spanish Ministry of Science and Innovation (PI19/00,672). CCZ was supported by the CAMH Foundation and by the Brain and Behavior Research Foundation. ISP was partially supported by a Sylvia B. Chase Early Career Research Award. The results published here are in part based on data obtained from the AD Knowledge Portal ( https://adknowledgeportal.org ). Study data were provided by the Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago. Data collection was supported through funding by NIA grants P30AG10161 (ROS) and RF1AG57473 (single nucleus RNAseq).

Publisher Copyright:
© 2021

ASJC Scopus Subject Areas

Pharmacology
Neurology
Clinical Neurology
Psychiatry and Mental health
Biological Psychiatry
Pharmacology (medical)

PubMed: MeSH publication types

Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.euroneuro.2021.12.003

Cite this

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title = "A review and meta-analysis of gene expression profiles in suicide",

abstract = "Suicide claims over 800,000 deaths worldwide, making it a serious public health problem. The etiopathophysiology of suicide remains unclear and is highly complex, and postmortem gene expression studies can offer insights into the molecular biological mechanism underlying suicide. In the current study, we conducted a meta-analysis of postmortem brain gene expression in relation to suicide. We identified five gene expression datasets for postmortem orbitofrontal, prefrontal, or dorsolateral prefrontal cortical brain regions from the Gene Expression Omnibus repository. After quality control, the total sample size was 380 (141 suicide deaths and 239 deaths from other causes). We performed the analyses using two meta-analytic approaches. We further performed pathway and cell-set enrichment analyses. We found reduced expression of the KCNJ2 (Potassium Inwardly Rectifying Channel Subfamily J Member 2), A2M (Alpha-2-Macroglobulin), AGT (Angiotensinogen), PMP2 (Peripheral Myelin Protein 2), and VEZF1 (Vascular Endothelial Zinc Finger 1) genes (FDR p<0.05). Our findings support the involvement of astrocytes, stress response, immune system, and microglia in suicide. These findings will require further validation in additional large datasets.",

author = "Piras, {Ignazio S.} and Huentelman, {Matthew J.} and Federica Pinna and Pasquale Paribello and Marco Solmi and Andrea Murru and Bernardo Carpiniello and Mirko Manchia and Zai, {Clement C.}",

note = "Funding Information: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. MM, FP, and BC gratefully acknowledge the support from FIR 2019 and FIR 2020 of the Department of Medical Sciences and Public Health, University of Cagliari. AM thanks the support of the Spanish Ministry of Science and Innovation (PI19/00,672). CCZ was supported by the CAMH Foundation and by the Brain and Behavior Research Foundation. ISP was partially supported by a Sylvia B. Chase Early Career Research Award. The results published here are in part based on data obtained from the AD Knowledge Portal (https://adknowledgeportal.org). Study data were provided by the Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago. Data collection was supported through funding by NIA grants P30AG10161 (ROS) and RF1AG57473 (single nucleus RNAseq). Funding Information: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. MM, FP, and BC gratefully acknowledge the support from FIR 2019 and FIR 2020 of the Department of Medical Sciences and Public Health, University of Cagliari. AM thanks the support of the Spanish Ministry of Science and Innovation (PI19/00,672). CCZ was supported by the CAMH Foundation and by the Brain and Behavior Research Foundation. ISP was partially supported by a Sylvia B. Chase Early Career Research Award. The results published here are in part based on data obtained from the AD Knowledge Portal ( https://adknowledgeportal.org ). Study data were provided by the Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago. Data collection was supported through funding by NIA grants P30AG10161 (ROS) and RF1AG57473 (single nucleus RNAseq). Publisher Copyright: {\textcopyright} 2021",

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AU - Solmi, Marco

AU - Murru, Andrea

AU - Carpiniello, Bernardo

AU - Manchia, Mirko

AU - Zai, Clement C.

N1 - Funding Information: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. MM, FP, and BC gratefully acknowledge the support from FIR 2019 and FIR 2020 of the Department of Medical Sciences and Public Health, University of Cagliari. AM thanks the support of the Spanish Ministry of Science and Innovation (PI19/00,672). CCZ was supported by the CAMH Foundation and by the Brain and Behavior Research Foundation. ISP was partially supported by a Sylvia B. Chase Early Career Research Award. The results published here are in part based on data obtained from the AD Knowledge Portal (https://adknowledgeportal.org). Study data were provided by the Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago. Data collection was supported through funding by NIA grants P30AG10161 (ROS) and RF1AG57473 (single nucleus RNAseq). Funding Information: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. MM, FP, and BC gratefully acknowledge the support from FIR 2019 and FIR 2020 of the Department of Medical Sciences and Public Health, University of Cagliari. AM thanks the support of the Spanish Ministry of Science and Innovation (PI19/00,672). CCZ was supported by the CAMH Foundation and by the Brain and Behavior Research Foundation. ISP was partially supported by a Sylvia B. Chase Early Career Research Award. The results published here are in part based on data obtained from the AD Knowledge Portal ( https://adknowledgeportal.org ). Study data were provided by the Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago. Data collection was supported through funding by NIA grants P30AG10161 (ROS) and RF1AG57473 (single nucleus RNAseq). Publisher Copyright: © 2021

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A review and meta-analysis of gene expression profiles in suicide

Abstract

Bibliographical note

ASJC Scopus Subject Areas

PubMed: MeSH publication types

UN SDGs

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